This application claims priority of International application number PCT/GB00/03931, filed Oct. 13, 2000, which in turn claims priority of British application number 9924374.3, filed Oct. 14, 1999, and British application number 9924375.0, filed Oct. 14, 1999.
This invention relates to a fluid-absorbing, composite material that is pressure-sensitive and comprises a continuous phase formed from a pressure-sensitive adhesive matrix and a discontinuous phase substantially comprised of one or more natural or synthetically derived water soluble and/or water insoluble absorbents.
Pressure sensitive adhesive materials are used in many medical device fields and are made into products such as tapes, bandages, surgical drapes, IV dressings and the like. Hydrocolloid pressure sensitive adhesives are medically useful adhesives that have been known for about 30 years and were originally developed as bandages for the oral cavity to aid in delivery of drugs to the gingiva. Hydrocolloid adhesives have been hitherto unique in that they are inherently adhesive and inherently absorbent. They are useful as wound dressings because they can be applied directly to open wounds and secured on the surrounding intact skin, and as skin barriers because they protect the peristomal skin of ostomy patients. Many hydrocolloid skin barriers are known and are used for these purposes. The more modern of these adhesives are xe2x80x9cintegratedxe2x80x9d. In this context, xe2x80x9cintegratedxe2x80x9d means those compositions that substantially retain their dimensional stability and form when saturated with wound exudate and/or other body fluid. xe2x80x9cNon-integratedxe2x80x9d means those compositions which become soft gels and amorphous as they become saturated with fluid. The shear strength of both integrated and non-integrated compositions can be improved using the teachings of the present invention, and the integrity of non-integrated compositions will also generally be increased.
The first hydrocolloid compositions to be described were non-integrated. U.S. Pat. No. 3,339,546 discloses compositions which are inelastic, and which are non-integrated, i.e. which do not maintain their dimensional stability and become amorphous when imbibed with wound fluid or other body fluid. A typical formulation taught by this prior art is the composition formed from low molecular weight polyisobutylene (40% by wt), pectin (20% by wt), sodium carboxymethyl cellulose (20% by wt) and gelatin (20% by wt). This formulation was used as a dressing for the gingiva but is also believed to be the basis of commercially successful skin barrier and wound care products. Such compositions form a soft gel when in contact with an exuding wound, and the resultant gel remains in the wound when the dressing is removed. This lack of integrity is a drawback. The gel must be removed from the wound at the time the dressing is changed. This is usually done by irrigation, which is time consuming for the nurse and painful for the patient. Adhesives taught by this patent also normally have relatively low shear strength, which can be a drawback in some use situations, particularly those in ostomy care, where the adhesive must retain on the abdomen a pouch containing body waste.
The lack of integrity was a serious drawback in the use of these dressings and barriers and much development was completed in efforts to overcome the deficiency. Thus, British Patent 1,576,522 corresponding to U.S. Pat. No. 4,231,369, describes improved hydrocolloid compositions that are integrated. There is provided a sealing material for ostomy use consisting of a hydrocolloid dispersed in a continuous phase of styrene-isoprene-styrene copolymer, or other thermoplastic elastomer such as an ethylene-propylene copolymer. Also present is a hydrocarbon tackifier and optionally an oil extender and an antioxidant. This material is said to have the advantage of being elastomeric and flexible. However, the absorption rate is lower than hydrocolloids made in accord with U.S. Pat. No. 3,339,546.
The shortcomings of barriers and dressings based upon formulae such as are described in U.S. Pat. No. 3,339,546 are also recognised by both U.S. Pat. No. 4,477,325 and U.S. Pat. No. 4,738,257. These two later patents disclose barriers and dressings based on an integrated formulation containing a continuous phase composed of a blend of high vinyl acetate EVA copolymer (51% wt VA and 49% wt ethylene) and low molecular weight polyisobutylene, in which is dispersed a discontinuous phase containing a blend of a superabsorbent material, pectin and sodium carboxymethyl cellulose. The function of the EVA copolymer is to cross link in the presence of ionising radiation, such as gamma radiation at a dosage of, for example, 25 KGy, which would be used to sterilise dressings formed from the compositions of the invention. The cross-linked network is formed essentially from the EVA polymer by irradiation of the EVA containing elastomeric phase. If the composition is to be used as an ostomy barrier, the gamma radiation is an expensive process to achieve integration, because ostomy products are not normally sold sterile. If the adhesive composition is used non-sterile, its shear strength is low.
U.S. Pat. No. 4,551,490 describes integrated hydrocolloid adhesives modified by diluting the amount of styrene-isoprene-styrene block copolymer present in the composition. The patent provides a medical grade pressure sensitive adhesive composition comprising a heterogeneous mixture of one or more polyisobutylenes or blends of polyisobutylenes and butyl rubber, one or more styrene radial or block copolymers, a tackifier, mineral oil and one or more water soluble and/or swellable hydrocolloid gums. It is believed that the polyisobutylenes, butyl rubber, mineral oil and tackifier serve to modify and plasticise predominantly the isoprene segment of the block/radial copolymer. In particular, the mineral oil is said to provide increased extensibility and aggressiveness of the adhesive. It is believed that the teachings of this patent form the basis of the commercially available hydrocolloid dressing products DuoDerm and Signa Dress. However, it has been found that the rates of absorption of saline with these compositions is very slow, and not very reproducible, and moreover very much less than the absorption levels available with the compositions of U.S. Pat. No. 3,339,546.
Our co-pending Application WO99/14282 describes a pressure sensitive adhesive material made of a weakly elastic mixture comprising a continuous phase formed from a blend of a physically cross-linked solid rubbers such as a styrene-isoprene-styrene triblock copolymer with a styrene-isoprene diblock copolymer, a compatible tackifying resin and a low molecular weight polyisobutylene, optionally modified by inclusion within the continuous phase of a quantity of butyl rubber, and a discontinuous phase comprising one or more hydrocolloids that are soluble and/or swellable in water. Small quantities of additives such as stabilisers and fumed silica may be present. The adhesive layer can be combined with a non-adhesive, water impervious film and can be used in wound care, ostomy care and in other medical products.
Our co-pending Application WO99/11728 describes a pressure sensitive adhesive material made of an elastic mixture comprising a continuous phase formed from a physically cross-linked solid rubber such as a styrene-isoprene-styrene block copolymer, and a compatible liquid rubber, such as a liquid styrene-isoprene rubber, and a discontinuous phase comprised of one or more absorbents that are swellable or soluble in water. Resinous materials are preferably absent, but additives such as polybutenes, polyisobutylene, mineral oil, stabilisers, and other rubbers, may be present. The pressure sensitive adhesives have the advantage over the prior art that they are extremely well integrated and contain no materials known to irritate skin and mucous membranes.
The composition of the present invention is characterised in that it contains 0.1 to 50% by weight, based on the continuous phase of trans-polyoctenamer.
The present invention provides compositions containing trans-polyoctenamer polymer that overcome some of the problems associated with the prior art. The present hydrocolloid adhesives have different and sometimes unique properties as compared to known hydrocolloid adhesives. Compositions may be formulated within the scope of the invention that have no leachable components that would contaminate a healing wound, and they can be used in wound care, ostomy care and other medical products. Within the scope of the invention, formulations can be prepared that have only weakly adhesive properties, also formulations that are suitable as primary dressings for various hard-to-heal and chronic wounds. By judicious choice of ingredients within the scope of the invention, compositions can be formulated that are relatively clear or translucent, and so are able to allow a visual assessment of the healing progress and the condition of a wound under a dressing.
One aspect of the present invention relates to barriers and wound dressings comprising a layer of absorbent adhesive coated on a non-adhesive, waterproof film. This construction is useful in a number of ways. One of these is for bandaging purposes, especially on movable body parts such as joints or on curved surfaces of the body. Wounds such as blisters, burns, venostasis ulcers and decubitus ulcers may advantageously be treated with the products of the invention. Another important use is for the protection of the skin around body openings, especially around the surgically created openings known as colostomies, ileostomies and urostomies.
Another aspect of the invention comprises fluid absorbable pressure sensitive adhesives that contain an antimicrobial agent such as silver sulfadiazine, quaternary ammonium compounds, povidone-iodine, and the like. Such agents may be advantageously incorporated into the formulations of the instant invention to yield absorbent adhesives that can be made into dressings or pads for infected or colonised wounds.
A further aspect of the present invention comprises fluid absorbable pressure sensitive adhesives that are only weakly adhesive, and that may lose most of this low level of adhesion as the formulation absorbs for example wound exudate. Such materials, formulated within the scope of the invention, are especially useful as pads for adhesive bandages and dressings, adhesive pads, surgical pads and the like. In this embodiment, the materials would generally be held in place on the body by other pressure sensitive adhesives, and would function as an island, or central pad attached to one side, the wound contacting side, of a carrier or backing or fabric. In this embodiment, formulations are envisaged that optionally may contain an effective amount of an antimicrobial or antibiotic substance.
Still another aspect of the present invention relates to integrated absorbent pressure sensitive adhesives that are processable at lower temperatures than prior art materials. The rubbery trans-polyoctenamer polymer may be incorporated into the formulations of the instant invention at relatively low temperatures, say at 80-90xc2x0 C. The thermoplastic elastomers of prior art integrated formulations must be processed at temperatures of at least 160xc2x0 C., and preferably under a nitrogen atmosphere, in order to melt the thermoplastic elastomer and plasticise it effectively. The trans-polyoctenamer polymer melts at much lower temperatures. At these lower processing temperature, fewer unwanted side reactions or thermal and oxidative degradation occurs and lower quantities of processing stabilisers can be used. This in turn minimises the amounts of potential trace irritants and allergens in the finished adhesive. Within the scope of the invention, the trans-polyoctenamer may be advantageously incorporated with or without the concomitant inclusion of other thermoplastic elastomers. The novel compositions gain improved shear strength in either case, and improved processability in the case where there is no accompanying additional thermoplastic elastomer in the formulation.
A fluid absorbing composition according to the invention comprises a continuous phase consisting of a mixture of a permanently tacky pressure sensitive adhesive and trans-polyoctenamer polymer and dispersed within the continuous phase a discontinuous phase of one or more water soluble and/or water swellable absorbent polymers.
The permanently tacky pressure sensitive adhesive component must be tacky at room temperature as well as at the skin temperature of patients. Also, the adhesive must be dermatologically acceptable, which means that after continuous contact with skin there is little adhesive residue upon removal and there is no significant reaction with the skin during the adhesion period. The adhesive strength of the continuous phase must be sufficient to adhere to the skin of the patient for the time determined by the use of the medical device of which the adhesive forms part. Suitable permanently tacky pressure sensitive adhesive components may be used singly or in admixture, and include natural rubber, polyisobutylene, styrene-diene block copolymers, styrene-hydrogenated diene block copolymers, butyl rubber, acrylic polymers, silicone rubber, polyurethane rubber, polyvinyl ether and other like substances.
Other ingredients such as tackifiers, plasticisers, and polymer stabilisers may be added to the continuous phase, to modify tack and optimise adhesion properties and to protect polymers from degradation during processing.
Trans-polyoctenamer is a crystalline metathesis polymer of cyclooctene with predominantly trans-isomeric double bonds. It is said to contain a mixture of linear polymer and macrocyclic groups within each polymer chain. The trans-polyoctenamer is exemplified by the materials Vestenamer 6213 and 8012, which are available from Hxc3xcls AG. The polymer as available from Hxc3xcls AG is said to contain 15% by weight of cyclic oligomers and 85% of acyclic polymer. The crystallinity of the polymer is thermally reversible and reforms very rapidly on cooling the polymer below its melting point. While the inventor does not wish to be bound by any particular theory of action, it is believed that the high ring content in the polymer chains serves to aid compatibility between otherwise incompatible elastomers. Also, the polymer crystallinity and the high ring content increases the amount of network formation within the permanently tacky pressure sensitive adhesive continous phase. Further, the low content of double bonds in the polymer improves the thermal and oxidative stability of the formulation, while the low viscosity of molten trans-polyoctenamer aids the processing of these materials. The trans-polyoctenamer is present in an amount corresponding to from 0.1% to 50% by weight of the continuous phase, preferably from 3% to about 25% by weight of the continuous phase.
The discontinuous phase comprises one or more hydrophilic polymers that are soluble or insoluble but swellable in water as the moisture-absorbing component. One or more swellable polymers may be present. Suitable insoluble swellable polymers include cross-linked sodium carboxymethyl cellulose, crystalline sodium carboxymethyl cellulose, cross-linked dextran and starch-acrylonitrile graft copolymer. The swellable polymer may also be a so-called xe2x80x9csuper absorbentxe2x80x9d material such as starch sodium polyacrylate. Other hydratable polymers such as gluten and polymers of methyl vinyl ether and maleic acid and derivatives thereof may also be included in the discontinuous phase. Suitable water soluble polymers include sodium carboxymethyl cellulose, pectin, gelatine, guar gum, locust bean gum, collagen, karaya gum and the like. The discontinuous phase should not normally exceed 70% of the total weight of the adhesive, and preferably does not exceed 60% by weight of the adhesive, and may be comprised of any combination of soluble and/or insoluble absorbents.
Optional fillers such as silica and pigments and optional active ingredients such as epidermal growth factors and antimicrobial compounds may also be incorporated into the compositions of the invention. Silver sulfadiazine and benzalkonium chloride represent non-limiting examples of such antimicrobial ingredients. Also essential oils such as, for example, lavender oil or tea tree oil may be added in amounts sufficient for efficacy. Other active ingredients such as those that provide a warming or cooling sensation to the skin, for example capsaicin or menthol, may be added. Optional skin moisturising ingredients such as urea and polyols may be incorporated into the formulations of the instant invention.
The adhesive compositions of the invention may be conveniently prepared as follows. The components of the continous phase such as polyisobutylene, solid rubber, for example a styrene-olefin-styrene copolymer and any liquid ingredients such as a liquid rubber or a plasticiser are blended together in a suitable mixer, normally a sigma blade or Z-blade mixer with an extruder discharge. If thermoplastic elastomers are used, the mixer will need to be heated to about 170xc2x0 C. A nitrogen flow of about 60 ml/sec through the mixer reduces the possibility of oxidative degradation of the rubber during processing. About 1 phr of a suitable stabiliser can be added at this stage. After blending of the rubbers, tackifiers, plasticisers etc. the mixer is usually cooled to 90-105xc2x0 C. and the powdery ingredients are charged to the mixer together with the other optional ingredients, if present, and blended in for a period of time, usually 20-30 min. If high molecular weight rubbers are used, they may need to be premasticated in the mixer, or premilled on a rubber mill. The fully mixed mass is then removed from the mixer and then extruded or pressed to the desired thickness, and then laminated to suitable substrates.
The trans-polyoctenamer may be added to the contents of the mixer at the prepolymer stage, or later at the time the components of the discontinuous phase are added. Since the trans-polyoctenamer melts at low temperatures, it is very easily incorporated into the formulations.
Other processing techniques such as coating of the adhesive formulations from a solvent slurry, may also be employed, especially if the desired coating weight is less than about 0.25 mm (250 xcexcm). A general procedure for this type of processing is given in U.S. Pat. No. 3,972,328, column 2, ll. 44-60, and also in U.S. Pat. No. 4,427,737, column 2, ll. 24-47. Specific process procedures are given for each of the examples below.
The formulations prepared in the examples were evaluated using a number of different test methods. Descriptions of these test methods follow.
Reverse tack of hydrocolloid adhesives is the maximum force necessary to remove a standard polyester strip brought into contact with the hydrocolloid without external force, from this hydrocolloid surface.
Procedure
Make the test panel self adhesive using double coated tape. Laminate the hydrocolloid adhesive on the test panel. Place the test panel with hydrocolloid in the lower clamp. Program the tensile tester. Place a polyester test strip of thickness 125 xcexcm (5 mils) and dimensions (21 cmxc3x972.54 cm) in the upper clamp, making sure that the total length of polyester under the clamp (loop) is 15 cm. Remove the release liner from hydrocolloid and start the measurement.
The reverse tack is the maximum force to remove the polyester strip from the hydrocolloid surface.
Peel adhesion on stainless steel (SS) is the average force to remove a hydrocolloid adhesive, laminated under specified conditions on a SS panel, from the SS panel at constant speed and at an angle of 90xc2x0.
Procedure
Clean the SS-panel with solvent. Cut a hydrocolloid sample of 25.4 mm width and reinforce with reinforcing tape, laminate a paper strip at one end of the hydrocolloid sample using an overlap of about 1 cm. Remove the liner from the hydrocolloid sample and laminate the sample on the SS-panel with a 450 gm. roller at a speed of 150 cm/min. Allow the sample to dwell for 1 minute. Place the paper strip in the upper clamp and the SS-panel on the lower clamp, making sure that the angle between peel direction and SS-panel is 90xc2x0. Start the measurement using a crosshead speed of 300 mm/min. The angle must be kept 90xc2x0 until the measurement is completed. The 90xc2x0 peel adhesion is the average force to remove the hydrocolloid strip from the SS-panel.
Static shear is the time necessary to remove a hydrocolloid adhesive, laminated on a stainless steel panel under specified conditions, from the test panel under influence of a specified weight.
Condition the hydrocolloid samples at 23xc2x11xc2x0 and 50xc2x12% relative humidity for 24 hours. Clean the SS shear panel with solvent. Cut a hydrocolloid strip of 25.4 mm width and 50 mm length. Reinforce the hydrocolloid strip with reinforcing tape. Laminate the hydrocolloid strip on the test panel using an overlap surface of 1 inch2. Protect the free hydrocolloid with release liner. Put a weight of 500 g on the laminate for 1 hour. Reinforce the free hydrocolloid adhesive zone with reinforcing plastic and perforate. Place the test panel with hydrocolloid on the shear bar using a shear weight of 500 g. Re-zero the registration-clock. Note the time on the clock when the measurement is completed.
To determine the amount of fluid uptake into a known surface of hydrocolloid adhesive.
Procedure
Laminate the double coated tape with release liner on the upper side of the cup (contact zone for hydrocolloid). Fill the cup with 30 ml NaCl solution (0.9% wt). Cut a sample of hydrocolloid of about the same size as the outer cup diameter. Weigh the sample (W1). Laminate the sample onto the cup, making sure that the seal between the hydrocolloid sample and the cup is water tight. Turn the cup upside down and put it in the oven at 37xc2x0 C. for 24 hours. Cool down. Remove the hydrocolloid from the cup and weigh (W2). Calculate the water fluid absorption (g/sqm.24 h) with the formula:
abs=(W2xe2x88x92W1)/0.002375
(surface contact zone salt solution/hydrocolloid=0.002375 sq. m)
The flow of the hydrocolloid under influence of a specified pressure and after a specified time, is measured.
Procedure
Condition the hydrocolloid samples at 23xc2x11xc2x0 C. and 50xc2x12% relative humidity for 24 hours. Cut 5 samples of hydrocolloid using a 35 mm circular die-cutter Put a silicone paper on top of a first glass plate. Arrange the 5 samples on the silicone paper in a way that pressure is distributed equally. Measure the diameter of each sample with callipers, mark the exact place where the measurement is done. Put a plastic disk on each sample. Put another silicone paper and two glass plates over the construction followed by a weight of 10 kg. After 24 hours, measure the diameter of the samples where they are marked. Calculate the % increase of diameter of the samples. The cold flow is the % increase of diameter after 24 hours exposure to 10 kg (for 5 samples).
The integrity of a hydrocolloid is defined as its ability to resist breakdown by biological fluids. The test measures the weight percentage of hydrocolloid retained after exposure to saline under specified conditions.
Procedure
Condition the hydrocolloid samples at 23xc2x11xc2x0 C. and 50xc2x12% relative humidity for 24 hours. Cut circular samples from the hydrocolloid sheet 2,54 cm diameter. Weigh and record the samples (Wi). Place each sample in a 120 ml (4 oz) bottles with screw caps (Vel Catalog Number 1198017) with 50 ml physiological saline (NaCl 0,9% wt in water), cap the bottles and agitate on a bottle shaker at 200 speed for a period of 18 hrs. Remove the samples and dry them in the circulating air oven at 50xc2x0 C. and 50% relative humidity until dry. This usually takes about 24 hours. Reweigh the sample (Wf). The Integrity Value of the sample is calculated using the following equation:       Integrity    ⁢          xe2x80x83        ⁢    Value    ⁢          xe2x80x83        ⁢          (      %      )        =      100    xc3x97                  (                  W          f                )                    (                  W          i                )            
Note: The test may be run with hydrocolloid with or without carrier. However, the result may be affected, and suitable control samples should always be included.